This chapter presents a state of the art summary of mastocytosis relation to its definition, biology, epidemiology, disease mechanisms, clinical signs, diagnosis, treatment and prognosis. Mastocytosis consists of several variants, including cutaneous mastocytosis, systemic mastocytosis mast cell sarcoma, and extracutaneous mastocytoma. As the most important mast cell clonal disorder, mastocytosis is characterized by the clonal proliferation of abnormal mast cells. Triggers for mastocytosis include physical factors, emotional factors, drugs, venoms, infectious diseases with fever, and other agents. Diagnosis of mastocytosis is based on clinical manifestations, serum tryptase level, radiographic investigation in affected site, histopathologic examination of tissue, bone marrow biopsy with immunohistochemical stains, flow cytometric evaluation of CD2 and CD25, and molecular analysis of c-kit. Mastocytosis in pediatric patients may regress at puberty, but mastocytosis in adults does not regress. In systemic mastocytosis, patients may experience episodes of severe symptoms.